The long-term objective of the Mayo Center for Cell Signaling in Gastroenterology (MCCSG) is to understand the signaling pathways that control the function of gastrointestinal cells in health and disease. The Center members are organized into three Mechanistic Research Theme interest groups: i.) signal transduction; ii.) membrane receptors and ion channels; and, iii.) genetics and gene regulation. Each Mechanistic Research Theme represents an important area of signaling research that is an area of tremendous strength at Mayo Clinic. Our global hypothesis is that rapid advances in clinical care for patients with digestive diseases requires strong support of basic science research to identify disease mechanisms and intermediate biomarkers for digestive diseases, and that these basic science discoveries will generate translational research opportunities resulting in clinical trials. The Center goals are to promote and enhance cell signaling research by: i.) fostering collaborative, multidisciplinary research both by expanding the technical and collaborative capabilities of established Gl scientists and by attracting investigators from other disciplines; ii.) developing and implementing a robust and diverse Scientific Enrichment Program that includes seminars, workshops, symposia, a visiting faculty program, mini-sabbaticals, and web-based curricula; iii.) identifying and nurturing development of new Gl investigators via a rigorously peer-reviewed, widely publicized Pilot and Feasibility Program; and, iv.) promoting synergistic interaction between the signaling research base and the clinical research expertise of Mayo Gl investigators through activities that support signaling-related research and promote translation of basic science discoveries into clinical research. The Center seeks to support the three Mechanistic Research Themes by creating a supportive infrastructure that makes technologies more easily accessible, provides technical expertise to members from experts in a particular technology, uses existing resources efficiently, and develops novel methodologies through three linked biomedical Center Cores. The proposed biomedical cores are the: i.) Clinical Core; ii.) Genetics Core; and, iii.) Optical Microscopy Core. These Cores were developed by Center leadership in response to detailed and thoughtful analysis of barriers to cell signaling research and Center member surveys. The Core's specific goals are to: i.) develop and/or exploit advanced methods in biospecimen acquisition, processing, and annotation to enhance biospecimen collection and accessibility for Center investigators; ii.) enhance Center member's access to and implementation of current and emerging key genetic technologies; and, iii.) provide Center members with reliable access to state-of-the-art microscopic technology and expertise that will facilitate investigations of the pathogenesis of gastrointestinal and liver diseases.